title: Development of solid dispersions of artemisinin for transdermal delivery.
abstract: Solid dispersions of the poorly soluble drug artemisinin were developed using polymer blends of polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG) with the aim of enhancing solubility and in vitro permeation of artemisinin through skin. Formulations were characterised using a combination of molecular dynamics (MD) simulations, differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). Solubility of artemisinin was determined in two solvents: de-ionised water and phosphate buffered saline (PBS; pH 7.4), while in vitro drug permeation studies were carried out using rabbit skin as a model membrane. MD simulations revealed miscibility between the drug and polymers. DSC confirmed the molecular dispersion of the drug in the polymer blend. Decrease in crystallinity of artemisinin with respect to polymer content and the absence of specific drug-polymer interactions were confirmed using XRD and FT-IR, respectively. The solubility of artemisinin was dramatically enhanced for the solid dispersions, as was the permeation of artemisinin from saturated solid-dispersion vehicles relative to that from saturated solutions of the pure drug. The study suggests that high energy solid forms of artemisinin could possibly enable transdermal delivery of artemisinin.
authors.affiliation: Pharmacy and Pharmaceutical Science, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK. Electronic address: y.shahzad@live.com.
authors.forename: Yasser
authors.initials: Y
authors.lastname: Shahzad
authors.forename: Sadia
authors.initials: S
authors.lastname: Sohail
authors.forename: Muhammad Sohail
authors.initials: MS
authors.lastname: Arshad
authors.forename: Talib
authors.initials: T
authors.lastname: Hussain
authors.forename: Syed Nisar Hussain
authors.initials: SN
authors.lastname: Shah
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000737:chemistry*; D037621:Artemisinins / Q000008:administration & dosage / Q000737:chemistry*; D008297:Male; D010539:Permeability; D011092:Polyethylene Glycols / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry; D011817:Rabbits; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D011145:Polyvinyls; D011759:Pyrrolidines; C505150:poly(N-vinylpyrrolidine); D011092:Polyethylene Glycols; C031327:artemisinin
keywords: Artemisinin; Miscibility; Molecular dynamics; Permeability coefficient; Solid dispersions; Solubility parameter